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Abstract Title:

Baicalein induces apoptosis via ROS-dependent activation of caspases in human bladder cancer 5637 cells.

Abstract Source:

Int J Oncol. 2016 Sep ;49(3):1009-18. Epub 2016 Aug 6. PMID: 27571890

Abstract Author(s):

Eun-Ok Choi, Cheol Park, Hye-Jin Hwang, Su Hyun Hong, Gi-Young Kim, Eun-Ju Cho, Wun-Jae Kim, Yung Hyun Choi

Article Affiliation:

Eun-Ok Choi

Abstract:

Baicalein is a flavonoid derived originally from the root of Scutellaria baicalensis Georgi, which has been used in Oriental medicines for treating various diseases. Although this compound has been reported to have anticancer activities in several human cancer cell lines, the therapeutic effects of baicalein on human bladder cancer and its mechanisms of action have not been extensively studied. This study investigated the proapoptotic effects of baicalein in human bladder cancer 5637 cells. For this study, cell viability and apoptosis were evaluated using the 3-(4,5-dimethylthia-zol-2-yl)-2,5-diphenyltetrazolium bromide assay, trypan blue dye exclusion assay 4,6-diamidino-2-phenylindole staining, and flow cytometry. Measurements of the mitochondrial membrane potential (MMP), caspase activity assays and western blots were conducted to determine whether 5637 cell death occurred by apoptosis. Treatment with baicalein resulted in a concentration-dependent growth inhibition coupled with apoptosis induction, as indicated by the results of nuclei morphology examination and flow cytometry analyses. The induction of the apoptotic cell death of 5637 cells by baicalein exhibited a correlation with the downregulation of members of the inhibitor of apoptosis protein (IAP) family, including cIAP-1 and cIAP-2, and the activation of caspase-9 and -3 accompanied by proteolytic degradation of poly(ADP-ribose)-polymerase. The study also showed that baicalein decreases the expression of the proapoptotic protein Bax, increases antiapoptotic Bcl-2 expression, and noticeably aggravates the loss of MMP. Concomitantly, the data showed that baicalein increases the levels of death receptors and their associated ligands and enhances the activation of caspase-8 and truncation of Bid. However, the pan-caspase inhibitor can reverse baicalein-induced apoptosis, demonstrating that it is a caspase-dependent pathway. Moreover, it was found that baicalein can induce the production of reactive oxygen species (ROS) and that pretreatment with the antioxidant N-acetyl-L-cysteine significantly attenuates the baicalein effects on the loss of MMP and activation of caspase. In addition, the blocking of ROS generation decreases the apoptotic activity and antiproliferative effect of baicalein, indicating that baicalein induces apoptosis of 5637 cells through the ROS-dependent activation of caspases.

Study Type : In Vitro Study
Additional Links
Pharmacological Actions : Apoptotic : CK(5217) : AC(3846)

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